tRF-29-79 regulates lung adenocarcinoma progression through mediating glutamine transporter SLC1A5.
Carcinogenesis
; 45(6): 409-423, 2024 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-38366384
ABSTRACT
In recent decades, considerable evidence has emerged indicating the involvement of tRNA-derived fragments (tRFs) in cancer progression through various mechanisms. However, the biological effects and mechanisms of tRFs in lung adenocarcinoma (LUAD) remain unclear. In this study, we screen out tRF-29-79, a 5'-tRF derived from tRNAGlyGCC, through profiling the tRF expressions in three pairs of LUAD tissues. We show that tRF-29-79 is downregulated in LUAD and downregulation of tRF-29-79 is associated with poorer prognosis. In vivo and in vitro assay reveal that tRF-29-79 inhibits proliferation, migration and invasion of LUAD cells. Mechanistically, we discovered that tRF-29-79 interacts with the RNA-binding protein PTBP1 and facilitates the transportation of PTBP1 from nucleus to cytoplasm, which regulates alternative splicing in the 3' untranslated region (UTR) of SLC1A5 pre-mRNA. Given that SLC1A5 is a core transporter of glutamine, we proved that tRF-29-79 mediate glutamine metabolism of LUAD through affecting the stability of SLC1A5 mRNA, thus exerts its anticancer function. In summary, our findings uncover the novel mechanism that tRF-29-79 participates in glutamine metabolism through interacting with PTBP1 and regulating alternative splicing in the 3' UTR of SLC1A5 pre-mRNA.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Progressão da Doença
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Sistema ASC de Transporte de Aminoácidos
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Proteína de Ligação a Regiões Ricas em Polipirimidinas
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Ribonucleoproteínas Nucleares Heterogêneas
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Proliferação de Células
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Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China